AWM: High Calcium (2006)
Women with disease states (including osteoporosis, assessed by DEXA) or use of medications known to influence calcium and bone metabolism.
Recruitment
Advertising in local newspapers was done every 6 months over a 3 year period. Screened through telephone interviews and questionnaires regarding medical and nutrition history. There were 10 - 15 women per group and 7 groups from 2000 - 2003.
Design
Subjects were to consume either a moderately energy-restricted diet or to maintain their body weight, and were randomly assigned to either high calcium or normal calcium group.
Blinding used (if applicable)
Double-blinded.
Intervention (if applicable)
Weight maintenance or weight loss diets with high or normal calcium. A standard multivitamin and mineral supplement providing 200 mg Ca/day was given to all subjects throughout the study to standardize nutritional status. In addition to this supplement, subjects received additional daily supplements of calcium citrate or placebo. Goal total calcium intakes were 1.2 g/day for normal calcium and 1.8 g/day for high calcium groups.
Statistical Analysis
The weight maintenance and weight loss groups and calcium intake level effects were assessed by using two-factor ANCOVA with the week 6 measurements examined as the dependent variable. Because of differences in baseline body weight, estrone, 25(OH)D, 1,25(OH)2D and sNTx between groups, these variables were included as covariates in the model. Because of the potential effect of age, season and year of recruitment on calcium absorption, these were also included as covariates. When appropriate, multiple comparisons were performed by using Tukey's post hoc test. In addition, the percentage change from baseline to week 6 was assessed (2-way ANCOVA). Pearson correlation coefficients, comparisons of regression lines, and stepwise multiple regressions were used to evaluate the associations between changes in the different variables measured. To evaluate the effect of season of recruitment on either baseline values or the changes, we conducted a separate analysis by using these variables as the independent factors (one-factor ANOVA). P < 0.05 was considered significant. Data are presented as mean +/- SD.
Timing of Measurements
Participants underwent 1 month stabilization period of weight maintenance and consumption of 1 g Ca/day. Subjects underwent weekly diet counseling and measurements were taken at baseline and after 6 weeks.
Dependent Variables
- Body weight
- True fractional calcium absorption (TFCA) through dual stable-isotope methods
- Fasting blood samples for serum concentrations of parathyroid hormone, estradiol, estrone, 25(OH)D, and 1,25 dihydroxyvitamin D measured through radioimmunoassay
- Second-morning-void urine samples assessed through high-resolution, inductively coupled plasma mass spectrometry, urinary calcium and creatinine also measured
- Markers of bone resorption (urinary pyridinium crosslinks, pyridinoline and deoxy pyridinoline) were measured with the use of HPLC after hydrolyzed samples were submitted to a prefractionation procedure
- Serum N-telopeptide of type I collagen (sNTx) measured using ELISA
- Bone formation evaluated by measuring serum osteocalcin with radioimmunoassay
Independent Variables
- Dietary interventions - subjects in weight loss group started on a standard nutrition education and and behavior modification weight-reduction program under RD supervision that included weekly instruction and 3-day dietary intake records. Diet counseling and sample collection was collected every 6 months (April or October) to minimize seasonal effects on Vitamin D. Weight loss was achieved through reduced energy intake and habitual exercise maintenance - women were required to lose > 2.5% body weight.
Control Variables
Initial N: 73 women
Attrition (final N): 57 women completed the study (78%). Weight loss group (n=32), weight maintenance group (n=25).
Age: Mean age was 61 +/- 5 years (range 52 - 75 years)
Ethnicity: Not mentioned.
Other relevant demographics: Initial BMI 26.9 +/- 1.9
Anthropometrics Women recruited after summer months presented with greater concentrations of serum 25(OH)D (P< 0.05) and lower concentrations of serum PTH (P < 0.02) and tended to show greater concentrations of urinary calcium excretion (P < 0.08) but the season did not affect calcium absorption. No other differences in baseline characteristics between groups.
Location: New Jersey
| Normal Ca, Wt Maint (n=15) | Normal Ca, Wt Loss (n=16) | High Ca, Wt Maint (n=10) | High Ca, Wt Loss (n=16) |
P value Ca Amount |
P value Group | |
| Body Wt (kg) | 68.4 +/- 7.5 | 71.2 +/- 7.1 | 70.9 +/- 5.5 | 67.9 +/- 5.7 | 0.3227 | <0.0001 |
| Total Ca Intake (mg/day) | 1047 +/- 144 | 973 +/- 237 | 1776 +/- 183 | 1803 +/- 190 | <0.0001 | 0.9820 |
| TFCA (%) | 21.5 +/- 6.6 | 20.6 +/- 5.5 | 24.0 +/- 8.1 | 19.4 +/- 6.3 | 0.6099 | 0.0617 |
| Ca absorption (mmol/day) | 5.6 +/- 1.9 | 4.9 +/- 1.2 | 10.7 +/- 4.0 | 8.7 +/- 3.0 | <0.0001 | 0.0532 |
| Ca absorption (mg/day) | 223.7 +/- 75.5 | 195.4 +/- 48.8 | 429.3 +/- 159.8 | 348.3 +/- 118.0 | ||
| Urine Ca (mmol/day) | 3.2 +/- 1.8 | 2.8 +/- 1.5 | 3.5 +/- 1.9 | 3.7 +/- 2.3 | 0.2594 | 0.7881 |
| Urine Ca (mg/day) | 128.6 +/- 72.1 | 111.6 +/- 59.7 | 140.4 +/- 77.0 | 146.3 +/- 90.7 | ||
| Estrone (pmol/L) | 77.8 +/- 28.5 | 40.7 +/- 10.4 | 48.9 +/- 19.6 | 46.3 +/- 24.4 | 0.3359 | 0.0137 |
| Estradiol (pmol/L) | 54.8 +/- 15.1 | 41.5 +/- 8.8 | 51.8 +/- 7.7 | 43.8 +/- 15.1 | 0.1720 | 0.1718 |
| 25(OH) vit D (nmol/L) | 98.4 +/- 26.0 | 94.6 +/- 27.7 | 80.1 +/- 16.2 | 76.9 +/- 18.2 | 0.1639 | 0.2239 |
| 1,25(OH)2 vit D (pmol/L) | 99.4 +/- 35.0 | 145.2 +/- 41.3 | 116.9 +/- 29.8 | 113.8 +/- 36.2 | 0.9663 | 0.0464 |
| PTH (pmol/L) | 3.7 +/- 1.3 | 2.8 +/- 1.7 | 3.0 +/- 1.8 | 3.0 +/- 2.0 | 0.6152 | 0.3708 |
| Osteocalcin (nmol/L) | 3.1 +/- 1.1 | 3.3 +/- 1.1 | 2.4 +/- 1.1 | 3.0 +/- 0.7 | 0.0655 | 0.3645 |
| PYD/creatinine (nmol/nmol) | 27.2 +/- 9.5 | 28.7 +/- 14.8 | 27.6 +/- 17.3 | 22.3 +/- 6.9 | 0.5467 | 0.4769 |
| DPD/creatinine (nmol/nmol) | 10.1 +/- 3.3 | 9.2 +/- 4.9 | 8.8 +/- 5.6 |
6.7 +/- 2.3 |
0.1071 |
0.0952 |
| sNTx (nmol BCE) | 15.6 +/- 8.6 | 14.5 +/- 4.8 | 15.3 +/- 4.8 |
13.4 +/- 5.4 |
0.9238 |
0.3554 |
Other Findings
Women allocated to weight loss group lost an average of 3.4 +/- 1.3 kg (4.7 +/- 1.8% of initial body weight). Women in the weight maintenance group maintained their weight within 0.3 +/- 1 kg.
There were no differences between the groups with the exception of energy, protein, fat, carbohydrates and calcium, as expected with the study design. For the normal calcium group, calcium intake was 1002 +/- 203 mg/day for weight maintenance and 973 +/- 237 mg/day for weight loss. For the high calcium group, calcium intake was 1776 +/- 183 mg/day for weight maintenance and 1803 +/- 190 mg/day for weight loss.
Baseline true fractional calcium absorption (TFCA) of 24.9 +/- 7.4%.
Energy restriction significantly decreased the total calcium absorbed (P < 0.05) in the weight loss group compared to the weight maintenance group.
Regression analysis showed that a greater rate of weight loss suppressed TFCA and the total calcium absorbed (P < 0.05) in the high calcium group.
The women in the normal calcium weight loss group absorbed inadequate amounts of calcium (195 +/- 49 mg/day), whereas the women in the high calcium weight loss group absorbed adequate amounts (348 +/- 118 mg/day).
Parathyroid hormone explained 22% of the variance in calcium absorbed in the normal calcium group only.
| Government: | NIH |
22% dropout rate. Study only 6 weeks long. All subjects not studied at the same time. Small numbers of subjects in each group.
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Quality Criteria Checklist: Primary Research
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| Relevance Questions | |||
| 1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
| 2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
| 3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
| 4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
| Validity Questions | |||
| 1. | Was the research question clearly stated? | Yes | |
| 1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
| 1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
| 1.3. | Were the target population and setting specified? | Yes | |
| 2. | Was the selection of study subjects/patients free from bias? | ??? | |
| 2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | Yes | |
| 2.2. | Were criteria applied equally to all study groups? | Yes | |
| 2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
| 2.4. | Were the subjects/patients a representative sample of the relevant population? | ??? | |
| 3. | Were study groups comparable? | ??? | |
| 3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
| 3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | Yes | |
| 3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | No | |
| 3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
| 3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | N/A | |
| 3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
| 4. | Was method of handling withdrawals described? | Yes | |
| 4.1. | Were follow-up methods described and the same for all groups? | Yes | |
| 4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
| 4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
| 4.4. | Were reasons for withdrawals similar across groups? | Yes | |
| 4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
| 5. | Was blinding used to prevent introduction of bias? | Yes | |
| 5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | Yes | |
| 5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
| 5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
| 5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | N/A | |
| 5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
| 6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | Yes | |
| 6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | Yes | |
| 6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
| 6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | ??? | |
| 6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
| 6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
| 6.6. | Were extra or unplanned treatments described? | Yes | |
| 6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
| 6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
| 7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
| 7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
| 7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
| 7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | ??? | |
| 7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
| 7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
| 7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
| 7.7. | Were the measurements conducted consistently across groups? | Yes | |
| 8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
| 8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
| 8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
| 8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
| 8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | N/A | |
| 8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | Yes | |
| 8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
| 8.7. | If negative findings, was a power calculation reported to address type 2 error? | N/A | |
| 9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
| 9.1. | Is there a discussion of findings? | Yes | |
| 9.2. | Are biases and study limitations identified and discussed? | Yes | |
| 10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
| 10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
| 10.2. | Was the study free from apparent conflict of interest? | Yes | |